Varenicline for Nicotine Addiction

(VR Trial)

Overseen By Norma Castro, MA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, San Diego

Disqualifiers: Severe cardiovascular disease, Seizures, Others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 days

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed project will include enrollment of 200 daily tobacco cigarette users, ages 22+, from the San Diego community. Participants will be assessed on the VR Nicotine Cue Exposure paradigm then randomized (stratified on age and sex) to receive varenicline (target dose 1mg twice daily) or placebo (n per group=100; total N=200). Following eight days of titration, participants will be assessed again on the VR Nicotine Cue Exposure paradigm. They will then be followed via mobile assessments for eight days on target dose of varenicline, and 30-days post assessment by phone, to assess short-term nicotine use behaviors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have any conditions that are contraindicated with varenicline, you may not be eligible to participate.

What data supports the effectiveness of the drug varenicline for nicotine addiction?

Research shows that varenicline is effective in helping people quit smoking, with studies indicating that those who used it were 2.7 to 3.1 times more likely to remain smoke-free compared to those who took a placebo. It also helps reduce cravings and withdrawal symptoms, making it a valuable aid for smoking cessation. ^{1 2 3 4 5}

Is varenicline safe for humans?

Varenicline, used to help people stop smoking, has been linked to some psychiatric side effects like depression and suicidal thoughts. There have also been reports of movement disorders after stopping the drug. While it is generally considered safe, these potential side effects should be discussed with a healthcare provider. ^{1 2 3 6 7}

How does the drug varenicline work for nicotine addiction?

Varenicline is unique because it works by partially activating the same receptors in the brain that nicotine does, which helps reduce cravings and withdrawal symptoms while also blocking nicotine from having its usual rewarding effects. This dual action makes it different from other treatments like nicotine replacement therapies or bupropion. ^{1 3 4 6 8}

Eligibility Criteria

This trial is for daily tobacco users aged 22 or older who smoke at least 5 cigarettes a day and have been doing so for over 3 years. Participants must be willing to follow the study procedures, take oral medication, and if they can become pregnant, use effective contraception.

Inclusion Criteria

I can take pills and will follow the medication schedule.

I have craved nicotine in the past week.

I am 22 years old or older.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants are assessed on the VR Nicotine Cue Exposure paradigm and randomized to receive varenicline or placebo

1 day

1 visit (in-person)

Titration

Participants undergo an 8-day titration period to reach the target dose of varenicline or placebo

8 days

1 visit (in-person) at the end of titration

Treatment

Participants continue at the target dose for eight additional days with mobile monitoring

8 days

Mobile assessments

Follow-up

Participants are monitored for short-term nicotine use behaviors via phone assessments

30 days

Phone assessments

Treatment Details

Interventions

• Placebo
• Varenicline Tartrate

Trial Overview The study tests whether Varenicline Tartrate helps reduce cravings in tobacco users compared to a placebo. It involves VR assessments of nicotine cues before and after taking the drug or placebo, followed by mobile check-ins and a final phone assessment after one month.

Participant Groups

Group I: Varenicline Experimental Treatment 1 Intervention

Following the baseline assessment, participants randomized to receive varenicline will complete an 8-day titration period to achieve the target dose. Titration of varenicline will be as follows: 0.5 mg once daily for Days 1-3, 0.5 mg twice daily for Days 4-7, and 1 mg twice daily on Day 8. Participants then return to the lab on Day 9 (or Days 10, 11 if necessary) for testing at the target dosage (1 mg twice daily) and continue at that dose for eight additional days (Days 10-17) for mobile monitoring.

Group II: Placebo Placebo Group 1 Intervention

Following the baseline assessment, participants randomized to receive placebo pill will follow the same dosing schedule as the active arm. They will return to the lab on Day 9 (or Days 10, 11 if necessary) for testing and continue at that dosing schedule for eight additional days (Days 10-17) for mobile monitoring.

Varenicline Tartrate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Chantix for:

• Smoking cessation

Approved in European Union as Champix for:

• Smoking cessation

Approved in Canada as Champix for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study of 2,682 patients using varenicline for smoking cessation, nausea and vomiting were the most common reasons for discontinuation and the most frequently reported adverse drug reactions, highlighting the need for patient monitoring regarding gastrointestinal side effects.

While some psychiatric events were reported, including anxiety and depression, all cases of suicidal behavior involved patients with prior psychiatric conditions, suggesting that clinicians should closely monitor individuals with such histories when prescribing varenicline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. Kasliwal, R., Wilton, LV., Shakir, SA.[2021]

In a real-world study involving 566 participants across four European countries, varenicline was found to be an effective smoking cessation aid, with a 64.6% quit rate by the end of the 12-week treatment period.

The safety profile of varenicline was acceptable, with the most common side effects being mild to moderate nausea (8.9%) and insomnia (2.9%), and only 3.4% of participants discontinued due to treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. Boudrez, H., Gratziou, C., Messig, M., et al.[2015]

Varenicline, a medication used to help people quit smoking, is known to have some psychiatric and behavioral side effects, including reports of tardive dyskinesia, although these were not previously documented in literature.

This study presents the first two documented cases of withdrawal emergent dyskinesias associated with varenicline, highlighting a potential safety concern for users of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Withdrawal-Emergent Dyskinesias following Varenicline Therapy. Toffey, BA., Rabin, M., Kurlan, R.[2020]

Varenicline, an FDA-approved medication for smoking cessation, significantly increases the chances of quitting smoking, with continuous abstinence rates 2.7 to 3.1 times higher than placebo over a 52-week period after 12 weeks of treatment.

In addition to helping smokers quit, varenicline reduces cravings and withdrawal symptoms, making it a valuable option for those looking to stop smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline: a review of its use as an aid to smoking cessation therapy. Keating, GM., Siddiqui, MA.[2018]

In a study of 50 veterans using varenicline for smoking cessation, only 30% successfully quit smoking, which is lower than the 44% success rate reported in premarketing studies.

The study found a significant association between underlying psychiatric disorders and treatment failure, with all patients who discontinued due to adverse drug events related to mood changes having a history of mental illness, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of varenicline in a veteran population with a high prevalence of mental illness. Purvis, TL., Mambourg, SE., Balvanz, TM., et al.[2015]

In a study of 12,159 patients, varenicline was associated with reported neuropsychiatric events, particularly anxiety, but no significant increase in these events was found over time, suggesting that the drug's safety profile remains largely stable.

While 7-17% of neuropsychiatric events were attributed to varenicline by general practitioners, the analysis did not raise significant safety concerns, indicating that further investigation is needed to clarify the relationship between varenicline and anxiety symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England. Buggy, Y., Cornelius, V., Fogg, C., et al.[2021]

In a review of ten randomized controlled trials involving 3091 participants, varenicline did not show a significant increase in overall psychiatric disorders compared to placebo, with an incidence of 10.7% in the varenicline group versus 9.7% in the placebo group.

While varenicline was associated with a higher incidence of sleep disorders, there were no reported cases of suicidal ideation or behavior in the analyzed studies, suggesting that varenicline is generally safe for smokers without current psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. Tonstad, S., Davies, S., Flammer, M., et al.[2022]

In a study of 70 patients with brain lesions, those who quit smoking after their injury (Quitters) did not show higher rates of depression compared to those who continued smoking (Non-Quitters), indicating that smoking cessation itself is not linked to increased depression in this population.

The findings suggest that the neuropsychiatric side effects associated with varenicline, such as depression, are likely due to the medication rather than the act of quitting smoking, as both groups exhibited similar levels of depression and related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking cessation after brain damage does not lead to increased depression: implications for understanding the psychiatric complications of varenicline. Tranel, D., McNutt, A., Bechara, A.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. [2015]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Withdrawal-Emergent Dyskinesias following Varenicline Therapy. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Varenicline: a review of its use as an aid to smoking cessation therapy. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of varenicline in a veteran population with a high prevalence of mental illness. [2015]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Smoking cessation after brain damage does not lead to increased depression: implications for understanding the psychiatric complications of varenicline. [2021]